Triple vs. Double Therapy in naïves HIV-Infected Patients (TRIDUNA)
14. august 2020 oppdatert av: Luis F. Lopez-Cortes, Hospitales Universitarios Virgen del Rocío
Effectiveness of a Dual Therapy (Dolutegravir + Lamivudine) on Reduction of the Viral Reservoir, Immune Recovery and Immune Activation Compared With a Triple Therapy (Dolutegravir + Tenofovir Alafenamide/Emtricitabine) in Treatment-naïve HIV-Infected Patients
The objective of this study is to clarify whether if starting antiretroviral treatment based on dual therapy (DTG + 3TC) could provide less control of residual HIV replication and, therefore, a detriment on immune activation and inflammation compared to starting with triple therapy, and could worsen the patients' long-term prognosis.
For this purpose, the investigator has designed a randomized clinical trial where will assess the immunological recovery (CD4+/CD8+), immune activation, proliferation, senescence and apoptosis in T lymphocytes CD4+ and CD8+ cells by flow cytometry, the immune activation of monocytes/ macrophages and plasma concentrations of various inflammatory mediators by ELISAS, and the thymic function, the cellular reservoir of HIV and the degree of HIV DNA transcription by digital dropped PCR.
Studieoversikt
Studietype
Intervensjonell
Registrering (Forventet)
70
Fase
- Fase 4
Kontakter og plasseringer
Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.
Studiesteder
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Seville, Spania, 41013
- Rekruttering
- Hospital Universitario Virgen del Rocío
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Ta kontakt med:
- Luis F Lopez-Cortes, MD, PhD
- Telefonnummer: 34 - 955013096
- E-post: lflopez@us.es
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Hovedetterforsker:
- Luis F Lopez-Cortes, MD, PhD
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Hovedetterforsker:
- Alicia Gutierrez-Valencia, Pharm D
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Underetterforsker:
- Pompeyo Viciana, MD, PhD
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Underetterforsker:
- Rosa Ruiz-Valderas, MD, PhD
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Underetterforsker:
- Juan R Castillo-Ferrando, MD, PhD
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Deltakelseskriterier
Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
18 år og eldre (Voksen, Eldre voksen)
Tar imot friske frivillige
Nei
Kjønn som er kvalifisert for studier
Alle
Beskrivelse
Inclusion Criteria:
- Treatment-naïve HIV-1-infected patients ≥ 18 years of age.
- Plasma HIV-1 RNA >5000 and <500.000 copies/ml.
- T lymphocyte CD4+ count in peripheral blood >200/μl.
Patients of childbearing age should consent to use a highly effective contraceptive method from 15 days before the time of inclusion of the study until 30 days after the end of it. It is considered a highly effective method:
- Complete abstinence from penile-vaginal intercourse from 2 weeks prior to administration of Investigational Product, throughout the study, and for at least 2 weeks after discontinuation of all study medications;
- Any intrauterine device with published data showing that the expected failure rate is <1% per year (not all intrauterine devices meet this criterion)
- Male partner sterilization confirmed prior to the female subject's entry into the study, and this male is the sole partner for that subject.
- Approved hormonal contraception.
- Any other method with published data showing that the expected failure rate is <1% per year.
- Signed written informed consent prior to inclusion.
Exclusion Criteria:
- Acute HIV infection
- T lymphocyte CD4+ count in peripheral blood ≤ 200/µl
- Active opportunistic infection.
- Pregnancy at inclusion or during the follow-up
- Active hepatitis C and/or B virus co-infection.
- ALT ≥ 5 times the ULN, or ALT ≥ 3xULN and bilirubin ≥ 1.5xULN (with >35% direct bilirubin).
- Unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, or persistent jaundice), cirrhosis, known biliary abnormalities (apart from hyperbilirubinemia or jaundice due to Gilbert's syndrome or asymptomatic gallstones).
- Subjects with severe hepatic impairment (Class C) as determined by Child-Pugh classification.
- Current or past disease that requires the use subsidiary of treatment with corticosteroids, immunomodulatory agents, interferon or chemotherapeutic agents.
- Any laboratory abnormality grade 3 or 4 according to the U.S. Department of Health and Human Services, National Institutes of Health, National Institute of Allergy and Infectious Diseases, Division of AIDS (Annex 3)
- Concomitant use of drugs with potential major interactions with the prescribed drugs according to the respective full prescribing information.
- Estimated creatinine clearance <50ml/min.
- History or presence of allergy to the study drugs or their components
Studieplan
Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Behandling
- Tildeling: Randomisert
- Intervensjonsmodell: Parallell tildeling
- Masking: Ingen (Open Label)
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
|---|---|
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Eksperimentell: Dual Therapy
Dolutegravir plus lamivudine
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Randomize to naive-treatment HIV-infected patients to receive dual o triple therapy as initial antiretroviral treatment
Andre navn:
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Aktiv komparator: Triple Therapy
Dolutegravir plus TAF/FTC
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Randomize to naive-treatment HIV-infected patients to receive dual o triple therapy as initial antiretroviral treatment
Andre navn:
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Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
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proviral HIV-DNA
Tidsramme: 48 and 96 weeks
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Mean changes in proviral HIV-DNA in PBMCs after 48 and 96 weeks of treatment
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48 and 96 weeks
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Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
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Immune Recovery
Tidsramme: 48 and 96 weeks
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Mean changes immune recovery assessed by CD4+/CD8+ T cell ratio.
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48 and 96 weeks
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Immune Activation
Tidsramme: 48 and 96 weeks
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Mean changes immune activation assessed by the expression of HLA-DR and CD38 in both of CD4+ and CD8+ T cells.
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48 and 96 weeks
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Monocytes Activation
Tidsramme: 48 and 96 weeks
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Mean changes monocytes activation (plasma sCD14 and sCD163).
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48 and 96 weeks
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Immunosenescense
Tidsramme: 48 and 96 weeks
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Mean changes expression of markers for recent thymic emigrants (CD31), proliferation (Ki67), dysfunction (PD-1), senescence (CD57), and apoptosis (annexin A) in both CD4+ and CD8+ T cells.
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48 and 96 weeks
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Inflammation
Tidsramme: 48 and 96 weeks
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Mean changes concentration of pro-inflammatory soluble mediator in plasma: TNF-α, IL-1β, IL-6, IP-10, IFN- γ, MIP-1α, MIP-1β, hsPCR y D-dímers.
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48 and 96 weeks
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Viral Reservoir
Tidsramme: 48 and 96 weeks
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Mean changes viral reservoir size, evaluated by proviral HIV-DNA and HIV-RNA in peripheral blood mononuclear cells (PBMC) and CD4+ T cells isolate.
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48 and 96 weeks
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Andre resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
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Semen
Tidsramme: 24 weeks
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Mean changes of HIV-RNA seminal plasma viral load
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24 weeks
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GALT
Tidsramme: 48 weeks
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Mean changes of viral reservoir assessed as proviral HIV-DNA and HIV-RNA in GALT
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48 weeks
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Samarbeidspartnere og etterforskere
Det er her du vil finne personer og organisasjoner som er involvert i denne studien.
Studierekorddatoer
Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.
Studer hoveddatoer
Studiestart (Faktiske)
10. mars 2020
Primær fullføring (Forventet)
1. januar 2022
Studiet fullført (Forventet)
1. mars 2023
Datoer for studieregistrering
Først innsendt
2. mars 2020
Først innsendt som oppfylte QC-kriteriene
2. mars 2020
Først lagt ut (Faktiske)
4. mars 2020
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
18. august 2020
Siste oppdatering sendt inn som oppfylte QC-kriteriene
14. august 2020
Sist bekreftet
1. august 2020
Mer informasjon
Begreper knyttet til denne studien
Ytterligere relevante MeSH-vilkår
Andre studie-ID-numre
- FIS-TAR-01-2019
Legemiddel- og utstyrsinformasjon, studiedokumenter
Studerer et amerikansk FDA-regulert medikamentprodukt
Nei
Studerer et amerikansk FDA-regulert enhetsprodukt
Nei
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